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Toxicity of Nanomaterials and Legacy Contaminants: Risks to the Environment and Human Health

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 20226

Special Issue Editors


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Guest Editor
1. Dept. Environmental Health, National Institute of Health Dr. Ricardo Jorge, Porto, Portugal
2. EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
Interests: environmental health; genotoxicology; human exposure assessment; hazard assessment; nanotoxicology

E-Mail Website
Guest Editor
1. Dept. Environmental Health, National Institute of Health Dr. Ricardo Jorge, Porto, Portugal
2. EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
Interests: engineered nanomaterials; nanosafety; in vitro toxicology; in vivo toxicology

E-Mail Website
Guest Editor
1. EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal
2. Dept. Environmental Health, National Institute of Health Dr. Ricardo Jorge, Porto, Portugal
3. CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida Norton de Matos, S/N, 4450-208 Matosinhos, Portugal
Interests: environmental toxicology; nanotoxicology; chemical mixture toxicology; in vitro toxicology; analytical toxicology

Special Issue Information

Dear Colleagues,

Application of engineered nanomaterials (ENM) in a variety of fields and their increasing use in healthcare and consumer products come with serious concerns about their environmental and human health impact. The small size of the ENM facilitates their entrance into cells as well as their transfer across epithelial cells to reach different sensitive target sites. Increasing evidence shows that ENM present several potential toxic effects at molecular, cellular and/or genetic levels. Despite the increasing number of studies focusing on potential nanotoxicity, there is still plenty of contradictory information and knowledge gaps on how ENM interact with environmental species and humans, their mechanisms of interaction with the cells, tissues and organs. This knowledge is fundamental to correctly appraise the toxicological profile of ENM and crucial to their safe use/application.

One major aspect that has been understudied are the interactions of ENM with other chemical contaminants or even other ENM. Released ENM will co-exist and likely interact with other legacy contaminants (organic and inorganic) and with other ENM, and these interactions will affect their characteristics, behavior, uptake, and toxicity.

Hence, this Special Issue is intended to provide the current state-of-the-art, challenges, and future directions of the assessment of the risks to the environment and human health of ENM single and ENM mixtures (ENM–ENM and ENM–other contaminants). Original research and critical review manuscripts on (but not limited to) the following topics are welcome: i) Relationship between ENM physicochemical properties (size, shape, surface chemistry, solubility, etc.) alone or in mixtures and their toxicity (cyto, immuno and genotoxic responses); ii) in vivo and in vitro (eco)toxicity testing of ENM and chemicals mixtures; iii) novel or improved protocols to conduct (eco)toxicity assessment of ENM and chemical mixtures.

Dr. Carla Costa
Guest Editor

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Keywords

  • Nanomaterials
  • Legacy contaminants
  • Toxicity testing
  • human health
  • Environment
  • Co-exposure
  • Combined effects

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Published Papers (7 papers)

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Editorial

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4 pages, 217 KiB  
Editorial
Editorial of Special Issue: The Toxicity of Nanomaterials and Legacy Contaminants: Risks to the Environment and Human Health
by Ana Teresa Reis, Carla Costa and Sónia Fraga
Int. J. Mol. Sci. 2023, 24(14), 11723; https://doi.org/10.3390/ijms241411723 - 21 Jul 2023
Cited by 1 | Viewed by 1084
Abstract
Nanotechnology and the incorporation of nanomaterials (NM) into everyday products help to solve problems in society and improve the quality of life, allowing for major advances in the technological, industrial, and medical fields [...] Full article

Research

Jump to: Editorial

18 pages, 3081 KiB  
Article
Unveiling the Toxicity of Fine and Nano-Sized Airborne Particles Generated from Industrial Thermal Spraying Processes in Human Alveolar Epithelial Cells
by Maria João Bessa, Fátima Brandão, Paul H. B. Fokkens, Daan L. A. C. Leseman, A. John F. Boere, Flemming R. Cassee, Apostolos Salmatonidis, Mar Viana, Eliseo Monfort, Sónia Fraga and João Paulo Teixeira
Int. J. Mol. Sci. 2022, 23(8), 4278; https://doi.org/10.3390/ijms23084278 - 13 Apr 2022
Cited by 2 | Viewed by 2244
Abstract
High-energy industrial processes have been associated with particle release into workplace air that can adversely affect workers’ health. The present study assessed the toxicity of incidental fine (PGFP) and nanoparticles (PGNP) emitted from atmospheric plasma (APS) and high-velocity oxy-fuel (HVOF) thermal spraying. Lactate [...] Read more.
High-energy industrial processes have been associated with particle release into workplace air that can adversely affect workers’ health. The present study assessed the toxicity of incidental fine (PGFP) and nanoparticles (PGNP) emitted from atmospheric plasma (APS) and high-velocity oxy-fuel (HVOF) thermal spraying. Lactate dehydrogenase (LDH) release, 2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) metabolisation, intracellular reactive oxygen species (ROS) levels, cell cycle changes, histone H2AX phosphorylation (γ-H2AX) and DNA damage were evaluated in human alveolar epithelial cells at 24 h after exposure. Overall, HVOF particles were the most cytotoxic to human alveolar cells, with cell viability half-maximal inhibitory concentration (IC50) values of 20.18 µg/cm2 and 1.79 µg/cm2 for PGFP and PGNP, respectively. Only the highest tested concentration of APS-PGFP caused a slight decrease in cell viability. Particle uptake, cell cycle arrest at S + G2/M and γ-H2AX augmentation were observed after exposure to all tested particles. However, higher levels of γ-H2AX were found in cells exposed to APS-derived particles (~16%), while cells exposed to HVOF particles exhibited increased levels of oxidative damage (~17% tail intensity) and ROS (~184%). Accordingly, APS and HVOF particles seem to exert their genotoxic effects by different mechanisms, highlighting that the health risks of these process-generated particles at industrial settings should not be underestimated. Full article
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22 pages, 1662 KiB  
Article
In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure
by Fernanda Rosário, Carla Costa, Cláudia B. Lopes, Ana C. Estrada, Daniela S. Tavares, Eduarda Pereira, João Paulo Teixeira and Ana Teresa Reis
Int. J. Mol. Sci. 2022, 23(5), 2737; https://doi.org/10.3390/ijms23052737 - 1 Mar 2022
Cited by 9 | Viewed by 2719
Abstract
Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential [...] Read more.
Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential of titanium dioxide nanoparticles (TiO2NPs 0.75–75 mg/L), cerium oxide nanoparticles (CeO2NPs 0.075–10 μg/L), arsenic (As 0.01–2.5 mg/L), and mercury (Hg 0.5–100 mg/L) on human hepatoma (HepG2) and neuroblastoma (SH-SY5Y) cells. Viability was assessed through WST-1 (24 h) and clonogenic (7 days) assays and it was affected in a dose-, time- and cell-dependent manner. Higher concentrations caused greater toxicity, while prolonged exposure caused inhibition of cell proliferation, even at low concentrations, for both cell lines. Cell cycle progression, explored by flow cytometry 24 h post-exposure, revealed that TiO2NPs, As and Hg but not CeO2NPs, changed the profiles of SH-SY5Y and HepG2 cells in a dose-dependent manner, and that the cell cycle was, overall, more affected by exposure to mixtures. Exposure to binary mixtures revealed either potentiation or antagonistic effects depending on the composition, cell type and time of exposure. These findings prove that joint toxicity of contaminants cannot be disregarded and must be further explored. Full article
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14 pages, 2089 KiB  
Article
Suitability of the In Vitro Cytokinesis-Block Micronucleus Test for Genotoxicity Assessment of TiO2 Nanoparticles on SH-SY5Y Cells
by Natalia Fernández-Bertólez, Fátima Brandão, Carla Costa, Eduardo Pásaro, João Paulo Teixeira, Blanca Laffon and Vanessa Valdiglesias
Int. J. Mol. Sci. 2021, 22(16), 8558; https://doi.org/10.3390/ijms22168558 - 9 Aug 2021
Cited by 7 | Viewed by 2249
Abstract
Standard toxicity tests might not be fully adequate for evaluating nanomaterials since their unique features are also responsible for unexpected interactions. The in vitro cytokinesis-block micronucleus (CBMN) test is recommended for genotoxicity testing, but cytochalasin-B (Cyt-B) may interfere with nanoparticles (NP), leading to [...] Read more.
Standard toxicity tests might not be fully adequate for evaluating nanomaterials since their unique features are also responsible for unexpected interactions. The in vitro cytokinesis-block micronucleus (CBMN) test is recommended for genotoxicity testing, but cytochalasin-B (Cyt-B) may interfere with nanoparticles (NP), leading to inaccurate results. Our objective was to determine whether Cyt-B could interfere with MN induction by TiO2 NP in human SH-SY5Y cells, as assessed by CBMN test. Cells were treated for 6 or 24 h, according to three treatment options: co-treatment with Cyt-B, post-treatment, and delayed co-treatment. Influence of Cyt-B on TiO2 NP cellular uptake and MN induction as evaluated by flow cytometry (FCMN) were also assessed. TiO2 NP were significantly internalized by cells, both in the absence and presence of Cyt-B, indicating that this chemical does not interfere with NP uptake. Dose-dependent increases in MN rates were observed in CBMN test after co-treatment. However, FCMN assay only showed a positive response when Cyt-B was added simultaneously with TiO2 NP, suggesting that Cyt-B might alter CBMN assay results. No differences were observed in the comparisons between the treatment options assessed, suggesting they are not adequate alternatives to avoid Cyt-B interference in the specific conditions tested. Full article
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20 pages, 7645 KiB  
Article
Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles
by Svetlana V. Klinova, Boris A. Katsnelson, Ilzira A. Minigalieva, Oksana P. Gerzen, Alexander A. Balakin, Ruslan V. Lisin, Ksenia A. Butova, Salavat R. Nabiev, Oleg N. Lookin, Leonid B. Katsnelson, Larisa I. Privalova, Daniil A. Kuznetsov, Vladimir Ya. Shur, Ekaterina V. Shishkina, Oleg H. Makeev, Irene E. Valamina, Vladimir G. Panov, Marina P. Sutunkova, Larisa V. Nikitina and Yuri L. Protsenko
Int. J. Mol. Sci. 2021, 22(7), 3466; https://doi.org/10.3390/ijms22073466 - 27 Mar 2021
Cited by 9 | Viewed by 2319
Abstract
Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right [...] Read more.
Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex. Full article
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18 pages, 3171 KiB  
Article
Contribution of Particle-Induced Lysosomal Membrane Hyperpolarization to Lysosomal Membrane Permeabilization
by Tahereh Ziglari, Zifan Wang and Andrij Holian
Int. J. Mol. Sci. 2021, 22(5), 2277; https://doi.org/10.3390/ijms22052277 - 25 Feb 2021
Cited by 16 | Viewed by 3386
Abstract
Lysosomal membrane permeabilization (LMP) has been proposed to precede nanoparticle-induced macrophage injury and NLRP3 inflammasome activation; however, the underlying mechanism(s) of LMP is unknown. We propose that nanoparticle-induced lysosomal hyperpolarization triggers LMP. In this study, a rapid non-invasive method was used to measure [...] Read more.
Lysosomal membrane permeabilization (LMP) has been proposed to precede nanoparticle-induced macrophage injury and NLRP3 inflammasome activation; however, the underlying mechanism(s) of LMP is unknown. We propose that nanoparticle-induced lysosomal hyperpolarization triggers LMP. In this study, a rapid non-invasive method was used to measure changes in lysosomal membrane potential of murine alveolar macrophages (AM) in response to a series of nanoparticles (ZnO, TiO2, and CeO2). Crystalline SiO2 (micron-sized) was used as a positive control. Changes in cytosolic potassium were measured using Asante potassium green 2. The results demonstrated that ZnO or SiO2 hyperpolarized the lysosomal membrane and decreased cytosolic potassium, suggesting increased lysosome permeability to potassium. Time-course experiments revealed that lysosomal hyperpolarization was an early event leading to LMP, NLRP3 activation, and cell death. In contrast, TiO2- or valinomycin-treated AM did not cause LMP unless high doses led to lysosomal hyperpolarization. Neither lysosomal hyperpolarization nor LMP was observed in CeO2-treated AM. These results suggested that a threshold of lysosomal membrane potential must be exceeded to cause LMP. Furthermore, inhibition of lysosomal hyperpolarization with Bafilomycin A1 blocked LMP and NLRP3 activation, suggesting a causal relation between lysosomal hyperpolarization and LMP. Full article
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25 pages, 2293 KiB  
Article
Mild Effects of Sunscreen Agents on a Marine Flatfish: Oxidative Stress, Energetic Profiles, Neurotoxicity and Behaviour in Response to Titanium Dioxide Nanoparticles and Oxybenzone
by Ana Carvalhais, Bárbara Pereira, Mariangela Sabato, Rafaela Seixas, Marina Dolbeth, Ana Marques, Sofia Guilherme, Patrícia Pereira, Mário Pacheco and Cláudia Mieiro
Int. J. Mol. Sci. 2021, 22(4), 1567; https://doi.org/10.3390/ijms22041567 - 4 Feb 2021
Cited by 22 | Viewed by 4971
Abstract
UV filters are potentially harmful to marine organisms. Given their worldwide dissemination and the scarcity of studies on marine fish, we evaluated the toxicity of an organic (oxybenzone) and an inorganic (titanium dioxide nanoparticles) UV filter, individually and in a binary mixture, in [...] Read more.
UV filters are potentially harmful to marine organisms. Given their worldwide dissemination and the scarcity of studies on marine fish, we evaluated the toxicity of an organic (oxybenzone) and an inorganic (titanium dioxide nanoparticles) UV filter, individually and in a binary mixture, in the turbot (Scophthalmus maximus). Fish were intraperitoneally injected and a multi-level assessment was carried out 3 and 7 days later. Oxybenzone and titanium dioxide nanoparticles induced mild effects on turbot, both isolated and in mixture. Neither oxidative stress (intestine, liver and kidney) nor neurotoxicity (brain) was found. However, liver metabolic function was altered after 7 days, suggesting the impairment of the aerobic metabolism. An increased motility rate in oxybenzone treatment was the only behavioural alteration (day 7). The intestine and liver were preferentially targeted, while kidney and brain were unaffected. Both infra- and supra-additive interactions were perceived, with a toxicodynamic nature, resulting either in favourable or unfavourable toxicological outcomes, which were markedly dependent on the organ, parameter and post-injection time. The combined exposure to the UV filters did not show a consistent increment in toxicity in comparison with the isolated exposures, which is an ecologically relevant finding providing key information towards the formulation of environmentally safe sunscreen products. Full article
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